The objective of this project is to use monoclonal antibodies to identify and characterize specific cell surface molecules of murine hematopoietic cells and to use these antibodies as probes to study hematopoietic differentiation. The Pgp-1 glycoprotein is present on a variety of hematopoietic cell lineages but is absent on most cells of the thymus. Only 5 to 20% of the cells in the thymus are Pgp-1+. We are studyingthe nature of these Pgp-1+ thymus cells, using assays for thymic stem cells, and are studying the ontogeny of Pgp-1+ cells in the thymus during fetal development. We are also studying the antigenic phenotype of the "preleukemic" cells of the bone marrow and the phenotype of early leukemic cells of the thymus to determine the relationship between these cells and the Pgp-1+ thymocyte or its progenitor in the bone marrow. Antibody against the transferrin receptor has been considered as a possible immunotherapeutic reagent. We have isolated a number of monoclonal antibodies against the murine transferrin receptor, some of which block cell growth. Mutants of lymphoma cell lines that escape the growth inhibitory action of the antibodies have been isolated. We are studying the genetic mechanisms by which these mutant cells arise and are using the mutants and the antibodies to study aspects of transferrin receptor function. (CS)